This invention relates generally to cancer diagnosis and therapy, and more specifically, to cancers associated with over- or underexpression of Bin1 or other members of the BAR family of adaptor proteins.
Bin1/Amphiphysin/RVS (BAR) proteins are a family of adaptor proteins implicated in a diverse set of cellular processes, including tumorigenesis, cell survival, differentiation, and nerve synaptic activity. BAR proteins share a common N-terminal BAR domain also termed the RVS domain. While BAR proteins share a common domain (BAR), they appear to have divergent physiological functions.
As one example, amphiphysin is a neuronal protein of this family which is implicated in synaptic vesicle endocytosis [Wigge and McMahon, Trends Neurosci. 21: 339–344 (1998)]. Amphiphysin is also a paraneoplastic autoimmune antigen in cancers of the breast, lung, and other tissues [Antoine et al., Arch. Neurol. 56: 172–177 (1999); Dropcho, Ann. Neurol. 39: 659–667 (1996); Folli et al., N. Engl. J. Med. 328: 546–51 (1993)].
Bin1 (Bridging INtegrator-1) is a second, ubiquitous BAR protein that was initially identified in mammalian cells through its ability to interact with and inhibit the oncogenic properties of c-Myc [Sakamuro et al., Nature Genet. 14: 69–77 (1996)]. Ubiquitous Bin1 isoforms that localize to the nucleus have tumor suppressor properties and have been implicated in growth control, differentiation, and programmed cell death [Mao et al., Genomics 56: 51–58 (1999); Prendergast, Oncogene 18: 2966–2986 (1999); Sakamuro et al. 1996, cited above; Wechsler-Reya et al., Mol. Cell. Biol. 18: 566–575 (1998)].
Other members of the BAR family include the yeast proteins RVS167 and RVS161, which are believed to have some negative role in cell growth regulation.
There exists a need in the art for compositions and methods useful for diagnosis and treatment of conditions characterized by inappropriate cell growth control, or disorders affecting cell survival, differentiation, endocytosis, and actin organization.